Static contraction and passive stretch of skeletal muscle elicits reflex increases in cardiovascular function and this response is termed the exercise pressor reflex. This reflex is mediated by the activation of mechanically and metabolically sensitive muscle afferents. Static muscle contraction activates both afferent populations, while passive stretch stimulates only mechanically sensitive fibers. The goal of this proposal is to further clarify which neurotransmitters and neuromodulators are released in the dorsal horn of the spinal cord from the primary afferents that mediate this reflex. Utilizing microdialysis, the neurochemistry of the dorsal horn, the site where muscle afferents synapse, can be investigated with a high degree of demarcation. Microdialysis will be used to deliver antagonists to glutamate into the dorsal horn of the spinal cord. Preliminary results show that when antagonists to glutamate are dialyzed into the dorsal horn, the reflex cardiovascular changes to static contraction and muscle stretch are blunted. This provides the foundation that the release of glutamate into the dorsal horn plays a role in mediating the exercise pressor reflex. Microdialysis, in conjunction with HPLC, will also be used to quantitate glutamate release in the dorsal horn of the spinal cord evoked by contraction and muscle stretch. In addition, the magnitude of glutamate release in response to muscle contraction and stretch can be compared to determine if mechanically or metabolically sensitive afferents preferentially release this neurotransmitter. Also, the influence of the dorsal horn administration of calcitonin gene--related peptide on the reflex responses and glutamate release elicited by muscle afferent activation will be determined. Furthermore, the effects of stimulating medullary sites, which project to the dorsal horn, on the reflex responses and glutamate release evoked by static contraction and passive stretch of skeletal muscle will be investigated. Thus, these studies should provide a further understanding of the dorsal horn neurochemistry involved in the reflex cardiovascular responses to muscle afferent activation. Also, these experiments may help elucidate which neurotransmitters are released from mechanically and metabolically sensitive muscle afferents. This, in turn, should provide information concerning the processing of sensory input at the spinal level. Further, these studies may provide insight into possible adaptations within the central nervous system in response to chronic sensory stress, such as exercise training.